tbuckley/cabot-search huggingface dataset:
COVID-19 vaccine effectiveness against SARS-CoV-2 infection during the Delta period, a nationwide study adjusting for chance of exposure, the Netherlands, July to December 2021
Authors: Catharina E van Ewijk, Marjolein N Kooijman, Ewout Fanoy, Stijn FH Raven, Marit Middeldorp, Anita Shah, Brechje de Gier, Hester E de Melker, Susan JM Hahné, Mirjam J Knol
Journal: Eurosurveillance (2022)

BackgroundDifferential SARS-CoV-2 exposure between vaccinated and unvaccinated individuals may confound vaccine effectiveness (VE) estimates.AimWe conducted a test-negative case-control study to determine VE against SARS-CoV-2 infection and the presence of confounding by SARS-CoV-2 exposure.MethodsWe included adults tested for SARS-CoV-2 at community facilities between 4 July and 8 December 2021 (circulation period of the Delta variant). The VE against SARS-CoV-2 infection after primary vaccination with an mRNA (Comirnaty or Spikevax) or vector-based vaccine (Vaxzevria or Janssen) was calculated using logistic regression adjusting for age, sex and calendar week (Model 1). We additionally adjusted for comorbidity and education level (Model 2) and SARS-CoV-2 exposure (number of close contacts, visiting busy locations, household size, face mask wearing, contact with SARS-CoV-2 case; Model 3). We stratified by age, vaccine type and time since vaccination.ResultsVE against infection (Model 3) was 64% (95% CI: 50-73), only slightly lower than in Models 1 (68%; 95% CI: 58-76) and 2 (67%; 95% CI: 56-75). Estimates stratified by age group, vaccine and time since vaccination remained similar: mRNA VE (Model 3) among people ≥ 50 years decreased significantly (p = 0.01) from 81% (95% CI: 66-91) at < 120 days to 61% (95% CI: 22-80) at ≥ 120 days after vaccination. It decreased from 83% to 59% in Model 1 and from 81% to 56% in Model 2.ConclusionSARS-CoV-2 exposure did not majorly confound the estimated COVID-19 VE against infection, suggesting that VE can be estimated accurately using routinely collected data without exposure information.
Evaluation of 11 commercially available PCR kits for the detection of monkeypox virus DNA, Berlin, July to September 2022
Authors: Janine Michel, Angelina Targosz, Thomas Rinner, Daniel Bourquain, Annika Brinkmann, Jilian Amber Sacks, Lars Schaade, Andreas Nitsche
Journal: Eurosurveillance (2022)

Before the international spread of monkeypox in May 2022, PCR kits for the detection of orthopoxviruses, and specifically monkeypox virus, were rarely available. Here we describe the evaluation of 11 recently developed commercially available PCR kits for the detection of monkeypox virus DNA. All tested kits are currently intended for research use only and clinical performance still needs to be assessed in more detail, but all were suitable for diagnostics of monkeypox virus, with variations in specificity rather than sensitivity.
NLRP1 activation by UVB: Shedding light on an enigmatic inflammasome
Authors: Andrew Sandstrom
Journal: The Journal of Experimental Medicine (2022)

In this issue of JEM, Jenster et al. (2022. J. Exp. Med. https://doi.org/10.1084/jem.20220837) investigate how UVB radiation promotes activation of the inflammatory immune sensor NLRP1, and in doing so uncover how NLRP1 recognizes a diverse range of ribotoxic stresses.
[89Zr]Zr-DFO-girentuximab and [18F]FDG PET/CT to Predict Watchful Waiting Duration in Patients with Metastatic Clear-cell Renal Cell Carcinoma
Authors: Sarah R. Verhoeff, Sjoukje F. Oosting, Sjoerd G. Elias, Suzanne C. van Es, Sophie L. Gerritse, Lindsay Angus, Sandra Heskamp, Ingrid M.E. Desar, C. Willemien Menke-van der Houven van Oordt, Astrid A.M. van der Veldt, Anne I.J. Arens, Adrienne H. Brouwers, Bertha Eisses, Peter F.A. Mulders, Otto S. Hoekstra, Gerben J.C. Zwezerijnen, Winette T.A. van der Graaf, Erik H.J.G. Aarntzen, Wim J.G. Oyen, Carla M.L. van Herpen
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Watchful waiting (WW) can be considered for patients with metastatic clear-cell renal cell carcinoma (mccRCC) with good or intermediate prognosis, especially those with &amp;lt;2 International Metastatic RCC Database Consortium criteria and ≤2 metastatic sites [referred to as watch and wait (“W&amp;W”) criteria]. The IMaging PAtients for Cancer drug SelecTion-Renal Cell Carcinoma study objective was to assess the predictive value of [18F]FDG PET/CT and [89Zr]Zr-DFO-girentuximab PET/CT for WW duration in patients with mccRCC. Experimental Design: Between February 2015 and March 2018, 48 patients were enrolled, including 40 evaluable patients with good (n = 14) and intermediate (n = 26) prognosis. Baseline contrast-enhanced CT, [18F]FDG and [89Zr]Zr-DFO-girentuximab PET/CT were performed. Primary endpoint was the time to disease progression warranting systemic treatment. Maximum standardized uptake values (SUVmax) were measured using lesions on CT images coregistered to PET/CT. High and low uptake groups were defined on the basis of median geometric mean SUVmax of RECIST-measurable lesions across patients. Results: The median WW time was 16.1 months [95% confidence interval (CI): 9.0–31.7]. The median WW period was shorter in patients with high [18F]FDG tumor uptake than those with low uptake (9.0 vs. 36.2 months; HR, 5.6; 95% CI: 2.4–14.7; P &amp;lt; 0.001). Patients with high [89Zr]Zr-DFO-girentuximab tumor uptake had a median WW period of 9.3 versus 21.3 months with low uptake (HR, 1.7; 95% CI: 0.9–3.3; P = 0.13). Patients with “W&amp;W criteria” had a longer median WW period of 21.3 compared with patients without: 9.3 months (HR, 1.9; 95% CI: 0.9–3.9; Pone-sided = 0.034). Adding [18F]FDG uptake to the “W&amp;W criteria” improved the prediction of WW duration (P &amp;lt; 0.001); whereas [89Zr]Zr-DFO-girentuximab did not (P = 0.53). Conclusions: In patients with good- or intermediate-risk mccRCC, low [18F]FDG uptake is associated with prolonged WW. This study shows the predictive value of the “W&amp;W criteria” for WW duration and shows the potential of [18F]FDG-PET/CT to further improve this.
Rates of Routine Cancer Screening and Diagnosis Before vs After the COVID-19 Pandemic
Authors: Allison H. Oakes, Kelly Boyce, Catherine Patton, Sanjula Jain
Journal: JAMA Oncology (2022)

This cross-sectional study analyzes patterns in the rates of routine screening and diagnosis for breast, cervical, and colorectal cancer before and after the COVID-19 pandemic.
Residential Racial and Economic Segregation and Cancer Mortality in the US—Speaking Out on Inequality and Injustice
Authors: Victoria L. Seewaldt, Robert A. Winn
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Perioperative Immune Checkpoint Inhibition in Early-Stage Non–Small Cell Lung Cancer
Authors: Aakash P. Desai, Jacob J. Adashek, Joshua E. Reuss, Howard (Jack) West, Aaron S. Mansfield
Journal: JAMA Oncology (2022)

Although cancer-related mortality continues to decline, lung cancer remains the No. 1 cause of cancer deaths in the US. Almost half of the patients with non-small cell lung cancer (NSCLC) are diagnosed with early-stage, local or regional disease and are at high risk of recurrence within 5 years of diagnosis.Immune checkpoint inhibitors (ICIs) have improved outcomes for patients with metastatic NSCLC and have recently been tested in multiple clinical trials to determine their efficacy in the neoadjuvant or adjuvant setting for patients with local or regional disease. The landscape for perioperative ICIs in lung cancer is evolving rapidly, with recently reported and soon to mature clinical trials; however, the recent data highlight the potential of ICIs to increase response rates and decrease rates of relapse in early stages of lung cancer. Concurrently, novel applications of cell-free DNA may guide perioperative management strategies.This article reviews the various approaches of incorporating perioperative use of immunotherapeutic agents for the treatment of early stages of NSCLC.
Association of Residential Racial and Economic Segregation With Cancer Mortality in the US
Authors: Lu Zhang, Rui Gong, Lu Shi, Ming Wen, Xiaoqian Sun, K. Robin Yabroff, Xuesong Han
Journal: JAMA Oncology (2022)

Residential segregation is a structural risk factor for poor cancer outcomes. Previous research examining the association of residential segregation with cancer outcomes was limited by older data, restricted geographic areas, and few cancer sites. To guide targeted interventions, a comprehensive evaluation of the association between segregation and cancer outcomes is needed.To examine the association of residential racial and economic segregation with cancer mortality at the US county level for all cancers combined and for the 13 cancer types that represent the top 10 causes of cancer deaths in males or females.This ecological study used county-level sociodemographic data from the 2015-2019 American Community Survey linked with 2015-2019 county-level mortality data. Data analysis was performed from September 2021 to April 2022.Residential racial and economic segregation measured by the Index of Concentration at the Extremes (ICE) and categorized into quintiles 1 (most deprived) through 5 (most privileged).Age-adjusted cancer mortality was the outcome. Multilevel linear mixed modeling was used to calculate the adjusted mortality rate ratio (aRR).A total of 3110 counties were included. The age-adjusted mortality rates of all cancers combined were 179.8, 177.3, 167.6, 159.6, and 146.1 per 100 000 population (P < .001 for trend) for the 5 ICE categories (most deprived to least deprived), respectively. Compared with the least deprived counties, aRRs for all cancers combined were 1.22 (95% CI, 1.20-1.24) for the most deprived counties, followed by 1.17 (95% CI, 1.15-1.19), 1.10 (95% CI, 1.09-1.12), and 1.06 (95% CI, 1.04-1.08) for the other 3 quintiles, respectively (P < .001 for trend). Segregation was associated with increased mortality from 12 of 13 selected cancer sites, in which aRRs ranged from 1.06 (95% CI, 1.02-1.09) for brain and other nervous system cancer to 1.49 (95% CI, 1.43-1.54) for lung and bronchus cancer.The findings of this ecological study suggest that residential racial and economic segregation is associated with higher cancer mortality at the county level, highlighting opportunities for geographically targeted cancer prevention and control efforts.
Association of Machine Learning–Based Assessment of Tumor-Infiltrating Lymphocytes on Standard Histologic Images With Outcomes of Immunotherapy in Patients With NSCLC
Authors: Mehrdad Rakaee, Elio Adib, Biagio Ricciuti, Lynette M. Sholl, Weiwei Shi, Joao V. Alessi, Alessio Cortellini, Claudia A. M. Fulgenzi, Patrizia Viola, David J. Pinato, Sayed Hashemi, Idris Bahce, Ilias Houda, Ezgi B. Ulas, Teodora Radonic, Juha P. Väyrynen, Elin Richardsen, Simin Jamaly, Sigve Andersen, Tom Donnem, Mark M. Awad, David J. Kwiatkowski
Journal: JAMA Oncology (2022)

Importance Currently, predictive biomarkers for response to immune checkpoint inhibitor (ICI) therapy in lung cancer are limited. Identifying such biomarkers would be useful to refine patient selection and guide precision therapy. Objective To develop a machine-learning (ML)-based tumor-infiltrating lymphocytes (TILs) scoring approach, and to evaluate TIL association with clinical outcomes in patients with advanced non–small cell lung cancer (NSCLC). Design, Setting, and Participants This multicenter retrospective discovery-validation cohort study included 685 ICI-treated patients with NSCLC with median follow-up of 38.1 and 43.3 months for the discovery (n = 446) and validation (n = 239) cohorts, respectively. Patients were treated between February 2014 and September 2021. We developed an ML automated method to count tumor, stroma, and TIL cells in whole-slide hematoxylin-eosin–stained images of NSCLC tumors. Tumor mutational burden (TMB) and programmed death ligand-1 (PD-L1) expression were assessed separately, and clinical response to ICI therapy was determined by medical record review. Data analysis was performed from June 2021 to April 2022. Exposures All patients received anti–PD-(L)1 monotherapy. Main Outcomes and Measures Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were determined by blinded medical record review. The area under curve (AUC) of TIL levels, TMB, and PD-L1 in predicting ICI response were calculated using ORR. Results Overall, there were 248 (56%) women in the discovery cohort and 97 (41%) in the validation cohort. In a multivariable analysis, high TIL level (≥250 cells/mm 2 ) was independently associated with ICI response in both the discovery (PFS: HR, 0.71; P = .006; OS: HR, 0.74; P = .03) and validation (PFS: HR = 0.80; P = .01; OS: HR = 0.75; P = .001) cohorts. Survival benefit was seen in both first- and subsequent-line ICI treatments in patients with NSCLC. In the discovery cohort, the combined models of TILs/PD-L1 or TMB/PD-L1 had additional specificity in differentiating ICI responders compared with PD-L1 alone. In the PD-L1 negative (&amp;amp;lt;1%) subgroup, TIL levels had superior classification accuracy for ICI response (AUC = 0.77) compared with TMB (AUC = 0.65). Conclusions and Relevance In these cohorts, TIL levels were robustly and independently associated with response to ICI treatment. Patient TIL assessment is relatively easily incorporated into the workflow of pathology laboratories at minimal additional cost, and may enhance precision therapy.
Combining PARP Inhibitor With Immunotherapy—Does the Promise of Preclinical Data Translate to Clinic?
Authors: Rajat Thawani, Shivaani Kummar
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
An Algorithm as a Biomarker for Response to Immune Checkpoint Inhibitor Therapy
Authors: David L. Rimm
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Error in Figure Axis Label
Authors: Miguel Martin
Journal: JAMA Oncology (2022)

Biagio Ricciuti, MD; Xinan Wang, PhD; Joao V. Alessi, MD; Hira Rizvi, BA; Navin R. Mahadevan, MD; Yvonne Y. Li, PhD; Andrew Polio, MD; James Lindsay, MD; Renato Umeton, PhD; Rileen Sinha, PhD; Natalie I. Vokes, MD; Gonzalo Recondo, MD, PhD; Giuseppe Lamberti, MD; Marissa Lawrence, BS; Victor R. Vaz, MD; Giulia C. Leonardi, MD; Andrew J. Plodkowski, MD; Hersh Gupta, BA; Andrew D. Cherniack, PhD; Michael Y. Tolstorukov, PhD; Bijaya Sharma, BS; Kristen D. Felt, MS; Justin F. Gainor, MD; Arvind Ravi, MD, PhD; Gad Getz, PhD; Kurt A. Schalper, MD, PhD; Brian Henick, MD; Patrick Forde, MD; Valsamo Anagnostou, MD, PhD; Pasi A. Jänne, MD; Eliezer M. Van Allen, MD; Mizuki Nishino, MD; Lynette M. Sholl, MD; David C. Christiani, MD, PhD; Xihong Lin, PhD; Scott J. Rodig, MD, PhD; Matthew D. Hellmann, MD; Mark M. Awad, MD, PhD
Abstract PR022: IL-17/IL-17RA signaling in the pancreatic epithelium upregulates CXCL5 and B7-H4 to promote tumorigenesis
Authors: Lourdes Susana Castro Pando, Florencia McAllister, Olivereen Le Roux, Erick Riquelme, Le Li
Journal: Cancer Research (2022)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the second leading cause of cancer-related mortality. PDAC characterized by its highly immunosuppressive fibro-cellular tumor microenvironment (TME), which forms early during pancreatic tumorigenesis. Our group has shown that IL-17 is required for the initiation and progression of pancreatic cancer, but we have not defined the cellular compartment, mechanisms and signaling involved in IL-17-mediated tumor promotion. We hypothesize that pancreatic epithelial IL-17/IL-17RA signaling, rather than hematopoietic signaling, is required for early pancreatic tumorigenesis through modulation of an immunosuppressive program. To test our hypothesis, we generated mice with Kras activated and IL-17RA deleted specifically from the pancreatic epithelial compartment (KC; IL-17rafl/fl). Also, we transplanted IL-17RA deficient (IL17ra-/-) bone marrow cells into KC mice so IL-17RA is deleted specifically from hematopoietic cells. We found that the deletion of IL-17RA in the epithelial compartment delays the formation of premalignant lesions, conversely the deletion of IL-17RA in the hematopoietic compartment shows no change in the development of pancreatic tumorigenesis. Suggesting that the IL-17/IL-17RA signaling is through the pancreatic epithelium. Moreover, IL-17RA deletion in the oncogenic epithelium causes an increasing of CD3+ and CD8+ while decreasing F4/80+ Cells in TME. Furthermore, Cxcl5 and B7-H4 Aare less expressed in premalignant lesion of KC; IL-17RAf/f mice. Cxcl5 is a cytokine involve in neutrophil recruitment while B7-H4 can inhibit T cell response. By in vitro studies we have found that IL-17 stabilize the mRNA of CXCL5. Further studies are needed to understand how IL-17 mediates signaling in the pancreatic oncogenic epithelium trough Cxcl5. Citation Format: Lourdes Susana Castro Pando, Florencia McAllister, Olivereen Le Roux, Erick Riquelme, Le Li. IL-17/IL-17RA signaling in the pancreatic epithelium upregulates CXCL5 and B7-H4 to promote tumorigenesis [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr PR022.
Abstract PR013: High sensitive mutation detection in liquid biopsy with duodenal fluid captures genetic mutations associated with pancreatic carcinogenesis
Authors: Yusuke Ono, Kenji Takahashi, Hidenori Karasaki, Yusuke Mizukami
Journal: Cancer Research (2022)

Abstract Background: Blood-based liquid biopsy for comprehensive genomic profiling is available for cancer patients; however, given the limited amount of tumor-derived DNA in plasma, it remained challenging to detect pancreatic ductal adenocarcinoma (PDA) at earlier stages. Here, we evaluated the mutation detection in DNA from the duodenal fluid as an alternative biospecimen obtained by a less-invasive approach relative to endoscopic biopsy. Methods: In 300 patients of PDA, IPMN, or other pancreatic diseases in seven institutions, we collected duodenal fluid containing pancreatic juice from the duodenal lumen through the endoscopic channel. Plasma was also collected, and DNA was extracted from both samples, and molecular barcode sequencing, which enabled the highly sensitive detection of low- frequent mutation, targeting five pancreatic cancer-associated genes, namely, KRAS, GNAS, TP53, CDKN2A, and SMAD4, were performed. Detected mutations were evaluated for concordance with surgically resected tissue or needle biopsy. Results: DNA extracted from the duodenal fluids (DFDNA) had a much higher yield (avg. 25.4 ng/ml) than plasma cell-free DNA (avg. 1.3 ng/ml). While plasma cfDNA had a typical fragmentation pattern with a peak at 160 bp, DFDNA has a variety of fragmentation patterns. Hotspot mutations detected in the duodenal fluids showed as much as 51.4% concordance with a 0.2 % the limit of detection (LOD) for its variant allele frequency in PDA-associated mutations in the DFDNA (n=109) with the mutations in PDA lesion, whereas only 25% concordance with 0.4% LOD in the plasma cfDNA (n=104). In contrast to plasma cfDNA, where liquid-tissue matches were limited to advanced stages of cancer, DFDNA assay enabled the higher concordance through a wide range of PDA stages, even Stage 0 (83.3%) or I (45.5%) UICC 8th, or IPMN cases, and allowed to detect of additional mutations that were originated from multicentric/concomitant lesions in the pancreas. Conclusions: Duodenal fluid-derived DNA can be a potent biospecimen to detect mutations with higher yield and sensitivity than plasma cfDNA. Although validation of the duodenal fluid collection and methods up to more sensitive analysis is required to meet the standards of practical testing, it has the potential to detect fast-stage pancreatic disease and the detection of lesions that were not visible on pathological images and is expected to lead to the implementation of highly sensitive liquid biopsy. Citation Format: Yusuke Ono, Kenji Takahashi, Hidenori Karasaki, Yusuke Mizukami. High sensitive mutation detection in liquid biopsy with duodenal fluid captures genetic mutations associated with pancreatic carcinogenesis [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr PR013.